Cell Death Flashcards
What are the differences between necrosis and apoptosis?
Necrosis produces an inflammatory response as cells burst and toxins leak out where as Apoptosis is carried out in a controlled manner without inflammation.
What are some key pathways that lead to apoptosis?
Embryology - lumen of tubes (via apoptosis)
Response to growth signal- menstrual cycle (via apoptosis)
Inflammation - resolution, death of neutrophils (via apoptosis)
Immune defence - T and Natural Killer cell responses. (via apoptosis)
Tumour prevention - prevent mutation (via apoptosis)
Autoimmune disease - self destruct (via apoptosis)
HIV AIDS - HIV and activated T cell death (via apoptosis)
What is the role of the Bcl2 family ?
They are involved in check and balances
BCL2 travels in pairs (homodimerise - 2 molecules travelling together that are the same) - The 2 BCL2 prevent cell death
Another member of the family is BAX also travel in a homodimerise fashion but they promote cell death. (they do this by triggering the intrinsic apoptotic pathway).
Cell dies or lives depending on the balance of this family.
How did caspases get their name ?
Caspases are key mediators
They get their name from;
• cysteine in the active site : “C”
• cleavage after aspartate: “asp”
• protease: “ase”
Define anoikis ?
An epithelial cell dies after losing contact with basement
membrane/extra cellular matrix
Can cause a tumour to spread as if it gains the ability to not require a basement membrane then it can travel and form a tumour.
Define pyroptosis ?
pyroptosis is an inflammatory form of programmed cell death that serves as a defense mechanism against infections, particularly those caused by pathogens like Salmonella.
Caspase 1 activation
What can caspases target?
- cleave ICAD -> destroy genetic information
- cleave PARP -> prevent DNA repair
- cleave lamin -> break down nuclear architecture
- cleave keratin -> break down cytoplasmic architecture
Why are apoptotic cells phagocytosed?
Keep
What is reversible cell injury ?
Reversible cell injury is a cell losing its ability to homeostasis but it has not died yet
What conditions to doctors work to save reversible cell injury and why is this important ?
In patients who have had stroke and heart attacks you have killed some cells but you have some cells around that which are sub-lethally injured and you can save them and reverse some symptoms
What toxin is produced from the electron transport chain ?
Oxygen becomes reactive due to electrons producing free radicals (O2-). These free radicals then become Hydrogen Peroxide (H2O2) which is damaging to cells.
What can free radicals cause?
Sublethal/leathal injuries to cells.
What happens in cells that have underwent lethal injury ?
Cells that experience lethal injury break normal homeostasis and necrosis occurs.
Seen in stroke and heart attacks as cells cannot produce energy and die.
How can a thrombus cause lethal injury ?
A thrombus prevents oxygenated blood from reaching Glycolysis in a cell and this causes Anaerobic glycolysis.
In anaerobic glycolysis a little ATP is made but so is Lactate which goes through a series of processes and activates phospholipases, which causes cell membrane damage, leading to cell necrosis.
What is Necrosis?
Necrosis is a complete loss of energy balance in a cell.
It is the death of tissues following bioenergetic failure and loss of plasma membrane integrity
It induces inflammation and repair due to toxins being outside the cell which aren’t wanted
Caused by ischaemia, metabolic, trauma
What are the 6 types of necrosis ?
- Coagulative necrosis in most tissues; firm pale area, with ghost outlines on microscopy
- Colliquative necrosis is seen in the brain; the dead area is liquefied
- Caseous necrosis is seen in tuberculosis; there is pale yellow semi-solid material
- Gangrene is necrosis with putrefaction: it follows vascular occlusion or certain infections and is black
- Fibrinoid necrosis is a microscopic feature in arterioles in malignant hypertension
- Fat necrosis may follow trauma and cause a mass, or may follow pancreatitis visible as multiple white spots
What is Apoptosis ?
A protective mechanism where you remove a cell in a controlled fashion.
The apoptotic body contains secondary lysosomes which break down cell material and trapped them in membranes which can be safely phagocytosed.
Apoptosis doesn’t cause inflammation as their membranes don’t let any water in so cells cannot burst
What is the difference between programmed cell death and apoptosis ?
Programmed cell death is an intention where as Apoptosis is a morphology (fragmentation and budding of cells).
What does Apoptosis usually involve the use of?
DNA fragmentation
What can we target in cancer chemotherapy to influence life or death of cells?
PARP (Poly ADP-RIbose polymerase)
ICAD (Inhibitor of caspase activated DNase)
How are apoptotic membranes removed and how is a apoptotic cell recognised?
Apoptotic cells (once they have fragmented) flip the lipids in their membrane (reorganisation of phosphatidylserine), which allows macrophages to recognise their phosphotidylserine signal and phagocytose them without an inflammatory response.
What is involved in extrinsic influenced apoptosis ?
Receptors and T cells are extrinsic factors which trigger apoptosis in cells
-Receptor Mediated-
What is involved in intrinsic influenced apoptosis ?
Stress, metabolic stress, DNA damage, Free radicals and p53 are intrinsic factors which trigger apoptosis in cells
- Intracellular stress -
What intrinsic factor is mutated and found in 50% of cancer patients?
gene for p53 in DNA - Can be caused by damage to DNA
